ASSESSMENT OF SAFETY AND MICROBIAL QUALITY OF COMPOUNDED CARBAMAZEPINE SYRUPS

Abstract

Abstract
Chemically, carbamazepine is 5H-dibenzo azepine-5-carboxamide. It is a highly lipophilic, neutral tricyclic molecule, crystalline powder that is practically odourless and white to off-white in colour. It is a sodium channel blocker that acts by deferential binding to energy-gated sodium channels in their inactive conformation. It is recommended for the treatment of generalized tonic-clonic seizures and partial seizures with simple or complicated symptomatology, trigeminal neuralgia, and bipolar disorder. This medication is readily available in tablet dosage forms and company manufactured liquid dosage forms as well. In the absence of the liquid dosage forms, the medication is extemporaneously prepared using readily available syrups as the vehicle. The compounded carbamazepine syrups have been used in practice but there is little information about the safety and quality. The aim of the study was to assess the microbiological quality of the compounded carbamazepine syrups and also study the safety by evaluating the effect of these preparations on kidney function, liver function, haematology and histopathology of laboratory rats. Microbiological quality of the formulations was evaluated by determining the total aerobic microbial count, total mold and yeast count, and identification of E. coli. The safety study was conducted by using laboratory rats which were grouped into treatment, positive control and negative control groups, where syrup compounded carbamazepine, distilled water compounded carbamazepine and distilled water were administered respectively for 28 consecutive days. The liver function test, kidney function test, hematological tests and histological examinations were all conducted and the findings were compared to reference/normal values. All the samples passed the microbiological quality test across the test period of 42 day for all the storage conditions. The rats
284 had normal levels of electrolyte, urea, creatinine, liver enzymes as well as total protein and albumin. Haematological parameters were also within the normal range. Histological examination of the kidney revealed normal findings corresponding to the kidney function test results. Liver histology was also basically normal, however cytoplasmic vacuolation was observed in the treatment and positive control groups which was linked to the drug metabolic activities. The findings suggest that compounded carbamazepine syrups had very good microbial quality and were found to be safe.